Methods for alleviating mucositis

ABSTRACT

The present invention is directed to a method for alleviating mucositis, sassociated with radiation and chemotherapy, via the administration of an oral rehydration solution.

[0001] This application is related to U.S. Ser. No. 60/315,598, whichwas filed on Aug. 29, 2001 (Atty. Docket No. 6834.US.Z1).

BACKGROUND

[0002] Chemotherapy and/or radiotherapy is effective at destroyingtumors because it targets the most rapidly growing tissues. Themechanism involves impairment of DNA synthesis or interference withmetabolic processes required for rapidly dividing cells. While tumorcells are selectively targeted by anticancer treatments, the mostrapidly growing tissues of the host are also susceptible to theseeffects. The mucosal epithelium of the alimentary tract has one of themost rapid rates of cell division of any body tissue, and is therefore amajor site of toxicity for anticancer regimens.

[0003] The linings of the mouth and esophagus are particularly sensitiveto chemotherapy and radiation. The oral ulcerations characteristic ofmucositis (also referred to as ‘stomatitis’) are a major clinicalproblem causing considerable pain, increased susceptibility to infectionand inability to eat. Damage to the intestinal lining also occurscommonly in the small bowel, and less frequently in the large bowel,leading to severe diarrhea and pain. (Verdi C J 1993 Cancer therapy andoral mucositis. An appraisal of drug prophylaxis. Drug Safety 9:185-195;Sonis S T 1993 Oral complications of cancer chemotherapy In VT DeVitaJr., S Hellman and S A Rosenberg (ed) Cancer, Principles and Practice ofOncology, pp 2385-2394. Philadelphia, J B Lippencott Co).

[0004] In general, mucositis appears within 5 to 10 days of the drug orradiation treatment and can last several weeks. The severity ofmucositis can limit subsequent doses of chemotherapy or radiation.Patients suffering mucositis may need several weeks, or more, ofintravenous feeding as a result of the mouth ulcers, cramps, extremepain, gut denuding, and severe diarrhea (Verdi 1993; Sonis 1993).

[0005] About 40% of all patients receiving chemotherapy developsignificant mucositis. Incidences of up to 100% occur with some forms ofchemotherapy or radiotherapy. Clinically significant mucositis developswith a range of standard chemotherapy drugs that are used, either aloneor in combination, to treat various cancers including those of thecolon, breast, prostate, head, neck and haemopoetic system. Examples ofdrugs that frequently cause direct mucositis include, but are notlimited to, alkylating agents such as mechlorethamine, melphalan andbusulphan, antimetabolites including cytarabine, floxuridine,5-fluorouracil, mercaptopurine, methotrexate and thioguanine, cytotoxicdrugs such as bleomycin, actinomycin-D, daunorubicin, cisplatin,etoposide, mitomycin, vinblastine and vincristine, and otherchemotherapy drugs such as hyroxyurea and procarbazine (Sonis 1993).Direct exposure of the alimentary tract to high-dose radiotherapy, asoccurs for example with total body irradiation, treatment of head andneck tumors or radiotherapy of abdominal tumors, will also cause a highincidence of mucositis.

[0006] One problem that is typically associated with mucositis isexcessive weight loss. The damage inflicted upon the oral mucosatypically makes it painful for the patient to eat. This in turn leads tomalnutrition, weight loss, and susceptibility to infections.

[0007] One current treatment for the pain associated with mucositis isoral morphine (Mayo Clinic). Oral morphine has several side effectsincluding drowsiness, nausea, and severe constipation. These sideeffects can interfere with both continuation of treatment and recoveryfrom treatment.

[0008] In addition to mucositis, loss of plasma potassium is typicallyassociated with chemotherapy and radiation due to the diarrhea andvomiting described above. To avoid hypokalemia, potassium tablets areoften given to the patient while they are undergoing chemotherapy. Whilethese tablets minimize hypokalemia, they are very irritating to thepatient's GI tract and can exacerbate the nausea and vomiting describedabove.

[0009] If the vomiting and diarrhea associated with chemotherapy becomessevere enough, patients can become severely dehydrated and experienceelectrolyte abnormalities. Such patients are often initiated on oralrehydration therapy after the occurrence of emesis and diarrhea. Forexample, Wadle reports that oral rehydration is typically initiated ifchemotherapy patients are experiencing diarrhea, Nursing clinics ofNorth America, December 1990, 25(4) page 901-908. Ippoliti also reportsthat after the occurrence of diarrhea, oral rehydration solutions shouldbe used in cancer patients to replace any fluid loss, AM. J.Health-Syst. Pharm. August 1998 55/15 (1573-1580).

[0010] While the medical literature does describe using oral rehydrationsolutions (ORS) in cancer patients, their role in cancer therapy issimilar to that of any patient experiencing diarrhea. ORS therapy isinitiated after the onset of diarrhea and vomiting. The ORS is used toreplace the water and electrolytes that the patient has lost. Themedical literature does not describe the use of ORS to alleviatemucositis, especially oral mucesitits. Nor does the medical literaturedescribe the prophylactic administration of ORS prior to the initiationof chemotherapy and/or radiation.

SUMMARY OF THE INVENTION

[0011] In accordance with the present invention, a new therapeutic usehas been discovered for oral rehydration solutions (ORS). It has beendiscovered that ORS will alleviate mucositis in patients undergoingcancer chemotherapy and/or radiation therapy. If consumed in sufficientquantities, the ORS will reduce reduce the physical discomfort thepatient experiences from the mucositis. This reduction in pain willallow the patient to consume a greater number of calories and will helpto alleviate the weight loss that is often associated with chemotherapy.Further, while the ORS will not prevent the occurrence of mucositis, itwill help to speed the rate at which the lesions heal.

[0012] In order to gain these benefits, the ORS needs to be consumed insufficient quantities. Typically, the patient will need to consume atleast 500 milliters of ORS daily, and more typically up to about 2000milliters. Consumption should be maintained until the pain from themucositis has dissipated

[0013] The ORS will also provide other benefits. The prophylacticadministration will help to maintain plasma potassium levels in a normalrange. This will decrease the need for potassium tablets and thegastrointestinal distress associated with these dosage forms. Further,maintaining an adequate state of hydration thru-out the patientstreatment will help the patient maintain their strength and vigorleading to an enhanced quality of life.

DETAILED DESCRIPTION OF THE INVENTION

[0014] As used herein:

[0015] a) one milliequivalent (mEq) refers to the number of ions insolution as determined by their concentration in a given volume. Thismeasure is expressed as the number of milliequivalents per liter(mEq/L). Milliequivalents may be converted to milligrams by multiplyingmEq by the atomic weight of the mineral and then dividing that number bythe valence of the mineral.

[0016] b) “ORS” or “ORS's” refers to oral rehydration solution(s). Forthe purposes of this invention, the term ORS should be construed asreferring to any composition containing at a minimum, glucose, sodiumand water; that would be considered suitable, by a medical professional,for use in rehydrating a patient who has experienced fluid andelectrolyte loss due to diarrhea. Beverages such as sport drinks (i.e.Gator-Aid), soft drinks (i.e. Coke or Pepsi), or kool-aid, should not beconsidered ORS's for the purpose of this invention. These beverages havea carbohydrate concentration in excess of 3.0 w/w % and would notfunction via the coupled transport mechanism described in detail below.

[0017] c) “mucositis” refers to toxic inflammatory reaction affedtiingthe gastrointestinal tract for mouth to anus, which may result fromexposure to chemotherapeutic or ionizing radiation. (NCI/PDQ PhysicianStatement: Oral complications of cancer and cancer therapy website6/2000). Specific examples include oral mucositis, esopagitis,enterititis and colitis.

[0018] d) “oral mucositis” and stomatitis should be considered synonomusand refer to mucositis impacting the oral cavity.

[0019] e) Any reference to a numerical range in this application shouldbe considered as being modified by the adjective “about”.

[0020] f) Any numerical range should be considered to provide supportfor a claim directed to a subset of that range. For example, adisclosure of a range of from 1 to 10 should be considered to providesupport in the specification and claims to any subset in that range(i.e. ranges of 2-9, 3-6, 4-5, 2.2-3.6, 2.1-9.9, etc.).

[0021] g) Any reference in the specification or claims to a quantity ofan electrolyte should be construed as referring to the finalconcentration of the electrolyte in the ORS. Tap water often containsresidual sodium, chlorine, etc. A value of 40 mEq of sodium, in thisapplication, means that the total sodium present in the ORS equals 40mEq, taking into account both added sodium as well as the sodium presentin the water used to manufacture the ORS. This holds true for allelectrolytes.

[0022] Oral rehydration solutions are well known to medicalprofessionals such as physicians, pharmacists, nurses, dieticians, etc.Oral rehydration solutions (ORS) are now routinely utilized throughoutthe world to correct the fluid and electrolyte losses associated withdiarrhea. They are used most prevalently in pediatric populations.

[0023] The principle underlying oral rehydration is the phenomenon ofcoupled transport. The presence of glucose in the ORS increases theabsorption of sodium by the body. Every glucose molecule that crossesthe intestinal epithelium brings a sodium ion with it, raising theconcentration of ions in the blood stream and pulling water out of thegut. The exact concentration of glucose in the oral fluid is veryimportant. Sodium absorption improves as the glucose concentration ofthe oral fluid is increased up to about 2.5% w/w. At higherconcentrations, the glucose can no longer be efficiently absorbedleading to a net reduction in sodium and water absorption. In fact,higher concentrations of glucose increase the osmotic load in the gut,which pulls water out of the blood stream. This leads to a net loss offluids and electrolytes which further exacerbates dehydration.

[0024] The World Health Organization recommended that an ORS contain 90mEq of sodium per liter, 20 mEq of potassium per liter, 30 mEq carbonateper liter and 111 mM of glucose per liter. Other ORS's containing loweramounts of sodium have been demonstrated to be equally effective. Forexample, the American Academy of Pediatrics Committee on Nutritionrecommendation for ORS is 40-60 mEq/L sodium, 20 mEq/L potassium, and2.0-2.5 wt./wt. % carbohydrate.

[0025] The ORS useful in this invention will contain all the necessaryelectrolytes and levels thereof required by the United States Food andDrug Administration for oral rehydration formulations sold in the UnitedStates. In addition to sodium (Na+), potassium (K+), chloride (Cl−) andcitrate ions, the ORS contains a source of carbohydrate, such asglucose, fructose, or dextrose. Typically, the ORS of this inventioncomprises water, carbohydrate, sodium ions, potassium ions, chlorideions, and citrate ions.

[0026] The quantity of sodium ions used in the ORS can vary widely, asis known to those skilled in the art. Typically, the ORS will containfrom about 30 mEq/L to about 95 mEq/L of sodium. In a furtherembodiment, sodium content can vary from about 30 mEq/L to about 70mEq/, most preferably from about 40 mEq/L to about 60 mEq/L. Suitablesodium sources include but are not limited to sodium chloride, sodiumcitrate, sodium bicarbonate, sodium carbonate, sodium hydroxide, andmixtures thereof

[0027] The ORS will also contain a source of potassium ions. Thequantity of potassium can vary widely. However, as a general guideline,the ORS will typically contain from about 10 mEq/L to about 30 mEq/L ofpotassium. In a further embodiment, it may contain from about 15 mEq/Lto about 25 mEq/L of potassium. Suitable potassium sources include butare not limited to, potassium citrate, potassium chloride, potassiumbicarbonate, potassium carbonate, potassium hydroxide, and mixturesthereof.

[0028] The ORS will also contain a source of carbohydrate. The quantityof carbohydrate utilized is important as described above. The quantitymust be maintained at less than about 3% w/w, and more preferably about2.5% w/w or less. Excessive carbohydrate will exacerbate the fluid andelectrolyte losses associated with diarrhea, that many cancer patientssuffer from.

[0029] Any carbohydrate used in prior art oral rehydration solutions maybe used to practice the present invention. Suitable carbohydratesinclude, but are not limited to, simple and complex carbohydrates,glucose, dextrose, fructoooligosaccharides, fructose and glucosepolymers, corn syrup, high fructose corn syrup, sucrose, maltodextrin,and mixtures thereof.

[0030] The ORS will also typically include a source of base. Typically,citrate will be incorporated into the ORS to accomplish this result.Citrate is metabolized to an equivalent amount of bicarbonate, the basein the blood that helps maintain acid-base balance. While citrate is thepreferred source of base, any base routinely incorporated intorehydration solutions may be used in the practice of the presentinvention.

[0031] The quantity of citrate can vary as is known in the art.Typically, the citrate content ranges from about 10 mEq/L to about 40mEq/L, more preferably from about 20 mEq/L to about 40 mEq/L, and mostpreferably from about 25 mEq/L to about 35 mEq/L. Suitable citratesources include, but are not limited to, potassium citrate, sodiumcitrate, citric acid and mixtures thereof.

[0032] The ORS will also typically contain a source of chloride. Thequantity of chloride can vary as is known in the art. Typically, the ORSwill contain chloride in the amount of from about 30 mEq/L to about 80mEq/L, more preferably from about 30 mEq/L to about 75 mEq/L, and mostpreferably from about 30 mEq/L to about 70 mEq/L. Suitable chloridesources include but are not limited to, sodium chloride, potassiumchloride and mixtures thereof.

[0033] Optionally, indigestible oligosaccharides may be incorporatedinto the ORS. Indigestible oligosaccharides have a beneficial impact onthe microbial flora of the GI tract. They help to suppress the growth ofpathogenic organisms such as Clostridium difficile. Theseoligosaccharides selectively promote the growth of a nonpathogenicmicrobial flora. Such ORS's have been described in U.S. Pat. No.5,733,759, filed Apr. 5, 1995, the contents of which are herebyincorporated by reference.

[0034] Typically, the oligosaccharide will be a fructoologosaccharide,an inulin such as raftilose, or a xylooligosaccharide. The quantity canvary widely, but may range from 1 to 100 grams per liter, and moretypically from 3 to 30 grams per liter of ORS.

[0035] Optionally, the ORS utilized in this invention may contain zinc.The quantity can vary widely, but will typically range from about 0.3mEq to about 95 mEq of zinc per liter of ORS. Typically, the ORS willcontain from about 0.6 mEq to about 3 mEq of zinc per liter.Alternatively, it may contain from about 0.6 mEq to about 1.2 mEq ofzinc per liter. The source of zinc ions is not critical. Any zinc saltsuitable for human consumption may be used in the ORS of this invention.Examples of suitable zinc sources include zinc gluconate, zinc sulfate,zinc chloride, zinc citrate, zinc bicarbonate, zinc carbonate, zinchydroxide, zinc lactate, zinc acetate, zinc fluoride, zinc bromide, andzinc sulfonate.

[0036] The ORS of the present invention will also typically include aflavor to enhance its palatability, especially in a pediatricpopulation. The flavor should mask the salty notes of the ORS. Usefulflavorings include, but are not limited to, cherry, orange, grape, fruitpunch, bubble gum, apple, raspberry and strawberry. Artificialsweeteners may be added to complement the flavor and mask the saltytaste. Useful artificial sweeteners include saccharin, nutrasweet,sucralose, acesulfane-K (ace-K), etc.

[0037] Preservatives may be added to help extend shelf life. Personsknowledgeable in the art would be able to select the appropriatepreservative, in the proper amount, to accomplish this result. Typicalpreservatives include, but are not limited to, potassium sorbate andsodium benzoate.

[0038] In addition to the carbohydrate described above, the ORS may alsocontain rice flour, or any other component of rice that is beneficial inthe treatment of diarrhea. Numerous rice supplemented ORS's have beendescribed in the literature. Methods for using such rice supplementedORS's are well known to those skilled in the art. Examples of such ricesupplemented ORS's include those described in U.S. Pat. No. 5,489,440issued Feb. 6, 1996; the contents of which are hereby incorporated byreference.

[0039] The ORS's utilized in this invention may also contain amino acidsor short peptides. For example, glutamine or derivatives thereof, may beincorporated into the ORS. For example, please refer to U.S. Pat. No.5,561,111, which is hereby incorporated by reference. Glutamine promoteshealing of the gut. The quantity of glutamine can vary but willtypically vary from 1 to 100 grams per liter, preferably about 6 grams.If desired ingredients such as glucosamine, chondrotin, hyaluronic acid,etc. can bee added to the ORS in quantities of about 1 to 100 grams perliter.

[0040] Arginine, or derivatives thereof, may also be incorporated intothe ORS. The quantity of arginine may vary, but will typically rangefrom 1 to 100 gram per liter.

[0041] The ORS of this invention can be manufactured using techniqueswell known to those skilled in the art. As a general guideline, all theingredients may be dry blended together; dispersed in water withagitation; and optionally heated to the appropriate temperature todissolve all the constituents. The ORS is then packaged and sterilizedto food grade standards as is known in the art. The package may containlabeling indicating that the product is suitable for alleviatingmucositis.

[0042] ORS may be administered in different forms, depending uponpatient preference, as is known in the art. For example, some patientswill consume ORS more readily if it is frozen, like a Popsicle. ORSpopsicles are described in detail in U.S. Pat. No. 5,869,459, thecontents of which are hereby incorporated by reference. The ORS of thissolution may be administered as frozen popsicles if the patient desiressuch a choice.

[0043] ORS's have also been formed into gels in order to enhance patientcompliance, especially in a pediatric population. The ORS of thisinvention may be gelled if desired. Gelled rehydration compositions aredescribed in U.S. patent application Ser. No. 09/368,388 filed Aug. 4,1999, the contents of which are hereby incorporated by reference. Thesegels have also been described in PCT Application No. 99/15862.

[0044] In summary, the ORS's useful in this invention are well known tothose skilled in the art. Any composition that would be considered anORS, by a medical professional, may be used in the present invention.The key to the present invention is that the inventors have discovered anew use for these ORS's. They have discovered that ORS can be used toalleviate mucositis.

[0045] The inventors are using the term “alleviate” to describe twobenefits that have been observed to date. First, the ORS reduces thediscomfort and pain that the patient experiences from the lesions,ulcers, and sores associated with mucositis. Aside from enhancing thepatient's quality of life, the reduced pain enables allows the patientto consume more calories and thus avoids the significant weight lossthat is typically associated with mucositis. Further, maintaining anormal diet significantly reduces the potential for the patient to beplaced on total parental nutrition (TPN) and the disruptions in lifestyle associated with such invasive therapy.

[0046] Secondly, the ORS accelerates the healing process, once thechemotherapy is completed. It has been discovered that the lesions andulcers heal at an accelerated rate in patients consuming ORS. The exactmechanism by which these benefits occurs is not understood, but thebenefits significantly improve the patients quality of life while theyare recovering from their cancer. Further, ORS has no known sideeffects, which further benefits the patients. Thus, the invention isdirected to the pallative support of oral mucositis and not to itsprevention.

[0047] In addition to alleviating ORS, the ORS has other benefits. Ithelps the patient maintain normal electrolyte levels thru-out theirtreatment, especially serum potassium levels. Maintaining adequatehydration also helps to fight fatigue.

[0048] In order to gain these benefits, it is necessary that the patientconsume sufficient quantities of the ORS. The exact quantity required toalleviate the mucositis will vary depending upon the severity of thepatient's mucositis, the chemotherapy and/or radiation regimen that thepatient is consuming, the patients age, the presence of other diseasesbesides cancer, etc. However, as a general guideline, at a minimum, thepatient should consume at least 500 milliliters daily. The solution canbe consumed in one sitting, but it is preferred if the patient graduallyconsumes the ORS on a periodic basis thru-out the day (i.e., 2-4 timesduring their waking hours). More preferably, the patient will consumefrom 1 to 3 liters daily, and most preferably about two liters daily.

[0049] ORS therapy can be initiated at any time during the patientschemotherapy. However, the most optimal benefits are obtained if thepatient begins consuming ORS prior to the time that chemotherapy orradiation therapy is initiated (i.e. prophylactically). Typically, thepatient will begin consuming the ORS about 1 day prior to the initiationof chemo/radio-therapy. More preferably, the ORS therapy will beginabout 3 days prior to chemo/radio therapy. Consumption of the ORS shouldbe maintained thru-out the course of chemo-/radio-therapy and maintaineduntil the lesions have healed sufficiently.

[0050] It is important to emphasize that while optimal benefits areobtained if ORS consumption is initiated prior to chemotherapy, benefitscan still be obtained for mucositis regardless of when therapy isinitiated. ORS consumption may be initiated at the same timechemo/radio-therapy is started, during such therapy, or at theconclusion of such therapy Thus the invention should be construed as theuse of ORS, at any time, to alleviate mucositis.

[0051] The following example is being presented in order to illustratethe invention. It should not be construed as limiting the invention inany manner.

EXAMPLE I Personal Testimony of Inventor

[0052] On January 14^(th), I received a stem cell transplant forMultiple Myeloma at the Mayo Clinic. From day one of chemotherapythrough the day of discharge fifteen days following, I consumed twoliters of unflavored Pedialyte daily. I had decided to consume Pedialyteto accelerate the healing after the destruction of thegatrointestinaltract from the high dose of Melphalan (200 mg/kg) used toablate the plasma cells. I consumed the first liter prior to breakfast.This hydrated my throat and gave some instant energy that allowed me toconsume my breakfast. I consumed my second liter around 5:00 p.m. Thiswas when my energy started to fade. The Pedialyte gave me another energyboost that allowed me to consume dinner.

[0053] I believe my clinical outcome was unique as compared to the otherpatients I was aware of going through the same treatment. I onlyrequired IV fluid one time during my entire stay as compared to almostdaily for others. My blood potassium and magnesium levels stayed normalfor the entire stay without the need for potassium supplements. Mostothers required potassium supplements and their magnesium levels did notstay normal. I had no need for hospitalization due to loss of fluid orweight for the entire stay as compared to at least once for most others.I lost no weight either during the stay or in the tow months since (Ihave gained 10 pounds). The normal is 5-6 pounds loss during the stayand up to another 20 pounds loss in the months following discharge. Mytotal treatment time was 15 days as compared to the average of 21 days.

[0054] Even the Mayo Clinic has not come up with anything to speedrecovery after such an aggressive procedure. I was told physicalrecovery post discharge would be 2-3 months. My physical recovery postdischarge from everything I can tell was 2-3 weeks.

We claim:
 1. A method for alleviating mucositis associated with cancerchemotherapy or radiation therapy comprising the administration to apatient in need thereof, of a sufficient quantity of a oral rehydrationsolution(ORS) containing a. from about 30 mEq to about 95 mEq of sodiumper liter; b. from about 10 mEq to about 30 mEq of potassium per liter;c. from about 10 mEq to about 40 mEq of citrate per liter, and; c. lessthan about 3.0 wt./wt. % of at least one carbohydrate.
 2. The methodaccording to claim 1 in which said patient consumes at least one-halfliter per day of said ORS.
 3. The method according to claim 1 in whichsaid patient initiates consumption of said ORS at least 24 hours priorthe initial chemotherapy or radiation treatment.
 4. The method accordingto claim 3 in which said patient consumes said ORS on a daily basiswhile undergoing said chemotherapy or said radiation therapy.
 5. Themethod according to claim 1 in which said ORS contains from about 0.3 toabout 95 mEq per liter of zinc.
 6. The method according to claim 1 inwhich said ORS contains 1 to 100 grams per liter of glutamine, or aderivative thereof.
 7. The method according to claim 1 in which saidaqueous solution contains chloride.
 8. The method according to claim 1in which said carbohydrate is a mixture of dextrose and fructose.
 9. Themethod according to claim 1 wherein said carbohydrate is present in aquantity of less than about 2.5 wt/wt %.
 10. The method according toclaim 1 in which said sodium is present in the quantity of about 30mEq/L to about 70 mEq/L.
 11. The method according to claim 1 whereinsaid sodium is selected from the group consisting of sodium chloride,sodium citrate, sodium bicarbonate, sodium carbonate, sodium hydroxideand mixtures thereof
 12. The method according to claim 1 in which saidpotassium is present in the quantity of about 10 mEq/L to about 30mEq/L.
 13. The method according to claim 1 wherein said potassium isselected from the group consisting of potassium citrate, potassiumchloride, potassium bicarbonate, potassium carbonate, potassiumhydroxide and mixtures thereof.
 14. The method according to claim 1 inwhich said ORS contains zinc.
 15. The method according to claim 14 inwhich said zinc is present in the quantity of from about 0.6 mEq/L toabout 5 mEq/L.
 16. The method according to claim 14 in which said zincis selected from the group consisting of zinc gluconate, zinc sulfonate,zinc chloride, zinc acetate, zinc sulfate, zinc citrate, zinc carbonate,zinc hydroxide, zinc lactate, zinc acetate, zinc fluoride, and zincbromide, zinc sulfonate.
 17. The method according to claim 1 in whichsaid ORS contains chloride in the quantity of from about 30 mEq/L toabout 80 mEq/L.
 18. The method according to claim 1 in which saidchloride is selected from the group consisting of potassium chloride,sodium chloride, and zinc chloride.
 19. The method according to claim 1in which said citrate is present in the quantity of from about 20 mEq/Lto about 40 mEq/L.
 20. The method according to claim 1 in which saidcitrate is selected from the group consisting of potassium citrate,sodium citrate, and citric acid.
 21. The method according to claim 1 inwhich said patient consume from about 1 liter to about 3 liters per dayof said ORS.
 22. The method according to claim 7 in which said patientinitiates consumption of said ORS about 1 week prior to the initiationto said chemotherapy or radiation therapy.
 23. A method for alleviatingthe weight loss associated with cancer chemotherapy or radiation therapycomprising the prophylactic administration to a patient of a sufficientquantity of a oral rehydration solution(ORS) containing a. from about 30mEq to about 95 mEq of sodium per liter; b. from about 10 mEq to about30 mEq of potassium per liter; c. from about 10 mEq to about 40 mEq ofcitrate per liter, and; d. less than about 3.0 wt./wt. % of at least onecarbohydrate.
 24. A method for reducing the side effects associated withcancer chemotherapy comprising the prophylactic administration to apatient of a sufficient quantity of a oral rehydration solution(ORS)containing a. from about 30 mEq to about 95 mEq of sodium per liter; b.from about 10 mEq to about 30 mEq of potassium per liter; c. from about10 mEq to about 40 mEq of citrate per liter, and; d. less than about 3.0wt./wt. % of at least one carbohydrate.
 25. The method according toclaim 10 in which said side effects is selected from the groupconsisting of oral mucositis, dysphagia, weight loss, loss of appetite,dehydration, loss of electrolytes, enteritis, and aphagia.
 26. Themethod according to claim 10 in which said side effects is selected fromthe group consisting of mucositis, dysphagia, enteritis, weight loss,loss of appetite, and aphagia.
 27. An article of manufacture comprisinga oral rehydration solution containing: a. from about 30 mEq to about 95mEq of sodium per liter; b. from about 10 mEq to about 30 mEq ofpotassium per liter; c. from about 10 mEq to about 40 mEq of citrate perliter, and; d. less than about 3.0 wt./wt. % of at least onecarbohydrate, in which said ORS is packaged in a container stating thatthe contents should be consumed by a patient to alleviate mucositis. 28.An article of manufacture comprising a oral rehydration solutioncontaining: a. from about 30 mEq to about 95 mEq of sodium per liter; b.from about 10 mEq to about 30 mEq of potassium per liter; c. from about10 mEq to about 40 mEq of citrate per liter, and; d. less than about 3.0wt./wt. % of at least one carbohydrate, in which said ORS is packaged ina container which is accompanied by an insert stating that the contentsmay be consumed by a patient to alleviate mucositis.